The Efficacy and Safety of Early Vitamin AD Supplementation in Very Preterm Infants

The Department of Neonatology, Zhengzhou Children's Hospital

Bronchopulmonary dysplasia (BPD) is the most prevalent longterm morbidity among surviving extremely preterm infants and has a multifactorial etiology. BPD is associated with later risk of reactive airways disease, such as asthma, post neonatal mortality and adverse neurodevelopmental outcomes.Retinopathy of prematurity (ROP) is a common retinal neovascular disorder and a major cause of vision impairment or blindness in preterm infants, even with aggressed current standard care.Accumulating epidemiologic evidence suggests that vitamin D (VD) deficiency or insufficiency is associated with respiratory disease and metabolic bone disease in premature children.Vitamin A (VA) plays an integral part in lung growth and differentiation. VA is an essential micronutrient for normal visual function.

Our prospective double-blinded randomized controlled trial will include infants born at <32 weeks' gestation and admitted to six tertiary NICUs in China. Infants in the intervention (vitamin AD drops) group will receive the daily dose VA at 1500 IU/day with VD 500 IU/day, added to their enteral feeds in drop form as soon as minimal feeding was introduced, and continued to 28 days or discharge. Infants in the control group will receive an equivalent volume of a placebo solution. Following informed consent, enrolled infants will be randomly allocated to the control or VAD group. The primary outcome is bronchopulmonary dysplasia (BPD) , ROP, or metabolic bone disease and the secondary outcomes are mortality; NEC ≥ stage 2; ; late-onset sepsis; weight gain, change in weight, increase in length, increase in head circumference; time to full enteral feeds; and number and type of critical incident reports.

Study Overview

• Status: Completed
• Conditions: Efficacy and Safety
• Intervention / Treatment: Other: Vitamin AD; Other: Control

• Study Type: Interventional
• Enrollment (Actual): 676
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450018
      • Zhengzhou Children'S Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 4 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• gestational age<32 weeks,
• <96 hours of age

Exclusion Criteria:

• genetic metabolic diseases;
• congenital major abnormalities;
• congenital non-bacterial infection with overt signs at birth;
• terminal stage of illness (pH < 7.0 or hypoxia with bradycardia>2 h);
• ≥ grade III intracranial hemorrhage;
• lacking parental consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin AD; In Vitamin AD group, the very preterm infants will receive the daily vitamin AD with vitamin A at1500 IU/day and vitamin D at 500 IU/day in drop form added to their enteral feeds when minimal feeding is introduced, and continue to 28 days or discharge. In this group ,the patient also will receive standard intravenous multivitamin preparation (1 ml/kg/d, containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.	Other: Vitamin AD; In Vitamin AD group, the very preterm infants will receive the daily vitamin AD with vitamin A at 1500 IU/day and vitamin D at 500 IU/day in drop form added to their enteral feeds when minimal feeding is introduced, and continue to 28 days or discharge. In this group ,the patient also will receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.
Placebo Comparator: Control; In this group ,the patient will only receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d,VD 80 IU/kg/d ) within daily on parenteral nutrition until fed 120ml/kg.	Other: Control; In this group ,the patient will only receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rates of bronchopulmonary dysplasia	The rates of bronchopulmonary dysplasia with early vitamin AD supplementation	1 year
rates of retinopathy of prematurity	The rates of retinopathy of prematurity with early vitamin AD supplementation	1 year
Metaboloc bone disease	The rates of Metaboloc bone disease of prematurity with early vitamin AD supplementation	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rates of Necrotizing enterocolitis	The rates of Necrotizing enterocolitis with early vitamin AD supplementation	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
rates of late-onset sepsis	The rates of late-onset sepsis with early vitamin AD supplementation	1 year

Collaborators and Investigators

• Sponsor: Zhengzhou Children's Hospital, China
• Investigators: Study Director: Shuying Luo, MD, Zhengzhou Children'S Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): June 28, 2020
• Study Completion (Actual): June 28, 2020

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 16, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): September 10, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins
• Other Study ID Numbers: VAD-PRETERM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No